Allogeneic cell therapies are a promising new technology for the treatment of a number of unmet medical needs. However, cell therapies are unique products and pose some unique challenges in the development process. One specific example of this technology is the development of human umbilical cord tissue-derived cells (“hUTC”) for a number of clinical indications. Following administration of hUTC to subjects, measuring the presence and/or the number of cells detected in the subject's blood is desirable information relevant to the pharmacokinetics of hUTC as a cell therapy product. However, this poses a challenge since hUTC may have characteristics that are similar to cells gathered from the blood of the subject. Therefore, it is necessary to distinguish hUTC from other cells.
Clinical studies during drug development include pharmacokinetic studies to examine parameters of absorption, distribution, metabolism, and excretion of the drug in vivo. An important element of the pharmacokinetic studies is to determine the level of exposure of a drug in subjects. Typically, this is done through analysis of drug levels from blood samples; exposure levels are evaluated relative to efficacy and safety outcomes. In the case of a cell therapy product, such as hUTC, studying the bio-distribution or pharmacokinetics of hUTC in clinical trials presents a challenge because there is no established method to distinguish hUTC (or other cell products) from the subjects' own cells. Therefore, it is difficult to determine the bioavailability of hUTC.
Presently accepted approach for determining if allogeneic therapeutic cells (e.g. hUTC) are present in the circulation requires the use of allogeneic therapeutic cells (e.g. hUTC) from a male donor and intravenous transfusion into female subjects. See e.g. Bader P. et al., “How and when should we monitor chimerism after allogeneic stem cell transplantation?” Bone Marrow Transplantation, 2005; 35: 107-119; see also Durnman, D M et al., “Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay,” Blood, 1989; 74: 2220-2226. Real time PCR is used to detect the Y chromosome in a sample of the subject's blood and the results provide a relative quantification or binary signal to indicate the presence or absence of allogeneic therapeutic cells (e.g. hUTC) in the blood sample. See Brader P. et al. This approach necessitates excluding female cell (e.g. hUTC) donors and male subjects from analyses on pharmacokinetics of hUTC in clinical studies. Therefore, there remains a need for a method for detecting allogeneic cells, such as e.g. UTC, in patients after administration of the cells.